Modern approaches to kidney cancer immunotherapy

Abstract

Kidney cancer is a heterogeneous group of malignant tumors that develop from cells of the proximal convoluted tubules of the kidney. In Russia renal cell carcinoma holds the 2nd place after prostate cancer among tumors of genitourinary system. The main method of renal cell carcinoma treatment is radical nephrectomy, at the same time, high resistance of kidney cancer to chemotherapy and a weak response to hormone treatment are noted, and the effectiveness of cytokine therapy (interleukin 2, interferon alfa) does not exceed 18–20 %. The introduction into clinical practice of modern immune system affecting drugs has changed the disease prognosis for many patients with various malignant neoplasms. Currently, active development of immunotherapeutic drugs directed against inhibitory receptors of T-cells, the so-called “immunity control points” takes place, the most studied among these drugs are anti-CTLA-4 (cytotoxic T-lymphocyte associated protein 4) and anti-PD-1 (рrogrammed cell death pathway 1)/PD-L1 (programmed death ligand 1) monoclonal antibodies. In this review a detailed description of the PD-1 receptor and its PD-L1 ligand, as well as the prognostic and predictive significance of their expression in various types of renal cell carcinoma and the role in suppressing the antitumor T-cell immune response are presented. Blockade of PD-1/PD-L1 enhances antitumor immunity reducing the amount and/or immunosuppressive activity of regulatory T-cells (suppressors) and restoring the activity of effector T-cells that leads to an enhancement of the antitumor immune response. The blockade of PD-1 also stimulates proliferation of memory B-cells. In this regard, drugs that suppress the function of PD-1 are now widely used in the treatment of cancer including kidney cancer. The authors provide a list of promising drugs acting on PD-1/PD-L1 system used in renal cell carcinoma: nivolumab, pembrolizumab and some others. The results of clinical studies se of immunotherapeutic drugs in kidney cancer are analyzed.